4 years ago

Stromal cell-derived factor-1α promotes endothelial colony forming cell migration through the Ca2+-dependent activation of the extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/AKT pathways.

Christian Andrea Di Buduo, Alessandra Balduini, Francesco Moccia, Dlzar Ali Kheder, Estella Zuccolo, Francesco Lodola, Valentina Poletto, Germano Guerra, Giorgia Scarpellino, Vittorio Rosti, Francesco Bertolini, Stefania Orecchioni
Stromal derived factor-1α (SDF-1α) drives endothelial colony forming cell (ECFC) homing and incorporation within neovessels, thereby restoring tissue perfusion in ischemic tissues and favouring tumor vascularization and metastasis. SDF-1α stimulates ECFC migration by activating the Gi-protein coupled receptor, CXCR4, and then engaging the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. Sporadic evidence showed that SDF-1α may also act through an increase in intracellular Ca2+ concentration ([Ca2+]i) in bone marrow-derived hematopoietic progenitor cells and fully differentiated endothelial cells. Of note, recent evidence demonstrated that intracellular Ca2+ signals play a key role in controlling the pro-angiogenic activity of ECFCs. The present investigation was, therefore, undertaken to assess whether and how SDF-1α induces ECFC motility by triggering intracellular Ca2+ signals. We found that SDF-1α caused a dose-dependent increase in [Ca2+]i that was inhibited by ADM3100, a selective CXCR4 antagonist. Pharmacological manipulation revealed that the Ca2+ response to [Ca2+]i was shaped by an initial intracellular Ca2+ release through inositol-1,4,5-trisphosphate receptors (InsP3Rs), followed by a sustained phase of extracellular Ca2+ entry through store-operated Ca2+ channels. InsP3-dependent Ca2+ release and store-operated Ca2+ entry (SOCE) were both necessary for SDF-1α-induced extracellular signal-regulated kinases 1/2 (ERK 1/2) and AKT phosphorylation. Finally, SDF-1α employed intracellular Ca2+ signals, ERK 1/2 and PI3K/AKT to promote ECFC migration in vitro and neovessel formation in vivo. These data, therefore, provide the first evidence that SDF-1α induces ECFC migration through the Ca2+-dependent activation of the ERK 1/2 and PI3K/AKT pathways.

Publisher URL: http://doi.org/10.1089/scd.2017.0114

DOI: 10.1089/scd.2017.0114

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.